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Lamin A/C cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation
AIMS: Lamin A/C (LMNA) mutations cause familial dilated cardiomyopathy (DCM) with frequent conduction blocks and arrhythmias. We explored the prevalence, cardiac penetrance, and expressivity of LMNA mutations among familial DCM in Norway. Furthermore, we explored the risk factors and the outcomes in...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5939624/ https://www.ncbi.nlm.nih.gov/pubmed/29095976 http://dx.doi.org/10.1093/eurheartj/ehx596 |
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author | Hasselberg, Nina Eide Haland, Trine Fink Saberniak, Jørg Brekke, Pål Haugar Berge, Knut Erik Leren, Trond Paul Edvardsen, Thor Haugaa, Kristina Hermann |
author_facet | Hasselberg, Nina Eide Haland, Trine Fink Saberniak, Jørg Brekke, Pål Haugar Berge, Knut Erik Leren, Trond Paul Edvardsen, Thor Haugaa, Kristina Hermann |
author_sort | Hasselberg, Nina Eide |
collection | PubMed |
description | AIMS: Lamin A/C (LMNA) mutations cause familial dilated cardiomyopathy (DCM) with frequent conduction blocks and arrhythmias. We explored the prevalence, cardiac penetrance, and expressivity of LMNA mutations among familial DCM in Norway. Furthermore, we explored the risk factors and the outcomes in LMNA patients. METHODS AND RESULTS: During 2003–15, genetic testing was performed in patients referred for familial DCM. LMNA genotype-positive subjects were examined by electrocardiography, Holter monitoring, cardiac magnetic resonance imaging, and echocardiography. A positive cardiac phenotype was defined as the presence of atrioventricular (AV) block, atrial fibrillation/flutter (AF), ventricular tachycardia (VT), and/or echocardiographic DCM. Heart transplantation was recorded and compared with non-ischaemic DCM of other origin. Of 561 unrelated familial DCM probands, 35 (6.2%) had an LMNA mutation. Family screening diagnosed an additional 93 LMNA genotype-positive family members. We clinically followed up 79 LMNA genotype-positive [age 42 ± 16 years, ejection fraction (EF) 45 ± 13%], including 44 (56%) with VT. Asymptomatic LMNA genotype-positive family members (age 31 ± 15 years) had a 9% annual incidence of a newly documented cardiac phenotype and 61% (19/31) of cardiac penetrance during 4.4 ± 2.9 years of follow-up. Ten (32%) had AV block, 7 (23%) AF, and 12 (39%) non-sustained VT. Heart transplantation was performed in 15 of 79 (19%) LMNA patients during 7.8 ± 6.3 years of follow-up. CONCLUSION: LMNA mutation prevalence was 6.2% of familial DCM in Norway. Cardiac penetrance was high in young asymptomatic LMNA genotype-positive family members with frequent AV block and VT, highlighting the importance of early family screening and cardiological follow-up. Nearly 20% of the LMNA patients required heart transplantation. |
format | Online Article Text |
id | pubmed-5939624 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-59396242018-05-10 Lamin A/C cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation Hasselberg, Nina Eide Haland, Trine Fink Saberniak, Jørg Brekke, Pål Haugar Berge, Knut Erik Leren, Trond Paul Edvardsen, Thor Haugaa, Kristina Hermann Eur Heart J Clinical Research AIMS: Lamin A/C (LMNA) mutations cause familial dilated cardiomyopathy (DCM) with frequent conduction blocks and arrhythmias. We explored the prevalence, cardiac penetrance, and expressivity of LMNA mutations among familial DCM in Norway. Furthermore, we explored the risk factors and the outcomes in LMNA patients. METHODS AND RESULTS: During 2003–15, genetic testing was performed in patients referred for familial DCM. LMNA genotype-positive subjects were examined by electrocardiography, Holter monitoring, cardiac magnetic resonance imaging, and echocardiography. A positive cardiac phenotype was defined as the presence of atrioventricular (AV) block, atrial fibrillation/flutter (AF), ventricular tachycardia (VT), and/or echocardiographic DCM. Heart transplantation was recorded and compared with non-ischaemic DCM of other origin. Of 561 unrelated familial DCM probands, 35 (6.2%) had an LMNA mutation. Family screening diagnosed an additional 93 LMNA genotype-positive family members. We clinically followed up 79 LMNA genotype-positive [age 42 ± 16 years, ejection fraction (EF) 45 ± 13%], including 44 (56%) with VT. Asymptomatic LMNA genotype-positive family members (age 31 ± 15 years) had a 9% annual incidence of a newly documented cardiac phenotype and 61% (19/31) of cardiac penetrance during 4.4 ± 2.9 years of follow-up. Ten (32%) had AV block, 7 (23%) AF, and 12 (39%) non-sustained VT. Heart transplantation was performed in 15 of 79 (19%) LMNA patients during 7.8 ± 6.3 years of follow-up. CONCLUSION: LMNA mutation prevalence was 6.2% of familial DCM in Norway. Cardiac penetrance was high in young asymptomatic LMNA genotype-positive family members with frequent AV block and VT, highlighting the importance of early family screening and cardiological follow-up. Nearly 20% of the LMNA patients required heart transplantation. Oxford University Press 2018-03-07 2017-10-31 /pmc/articles/PMC5939624/ /pubmed/29095976 http://dx.doi.org/10.1093/eurheartj/ehx596 Text en © The Author 2017. Published by Oxford University Press on behalf of the European Society of Cardiology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Clinical Research Hasselberg, Nina Eide Haland, Trine Fink Saberniak, Jørg Brekke, Pål Haugar Berge, Knut Erik Leren, Trond Paul Edvardsen, Thor Haugaa, Kristina Hermann Lamin A/C cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation |
title | Lamin A/C cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation |
title_full | Lamin A/C cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation |
title_fullStr | Lamin A/C cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation |
title_full_unstemmed | Lamin A/C cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation |
title_short | Lamin A/C cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation |
title_sort | lamin a/c cardiomyopathy: young onset, high penetrance, and frequent need for heart transplantation |
topic | Clinical Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5939624/ https://www.ncbi.nlm.nih.gov/pubmed/29095976 http://dx.doi.org/10.1093/eurheartj/ehx596 |
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